The purposes of this project are to characterize the interrelations between an acute infectious illness and carbohydrate metabolism: 1. Peripheral Mechanisms of Impaired Carbohydrate Metabolism during infection. (a) We have already demonstrated antagonism of insulin action by hormones secreted in excess quantities during viral infection in non diabetic normal volunteers. (b) These studies will be extended in this project to study the influence of acute infectious illnesses on glucose tolerance and on the regulation of plasma insulin, growth hormone, glucagon, ACTH, and cortisol secretion in patients with adult onset diabetes mellitus. 2. Direct (Pancreatic) Mechanisms of Impaired Carbohydrate Metabolism during infection. (a) Hamsters inoculated with the TC-83 vaccine strain of Venezuelan Encephalitis Virus (VEE) exhibit impaired glucose tolerance and insulin release following a glucose load (up to 10 weeks after viral inoculation). (b) Studies outlined here are designed to determine the duration of these abnormalities, the influence of nutritional factors, ultrastructural correlates of impaired insulin release, and the influence of VEE on glucagon secretion. (c) VEE studies (glucose tolerance, glucoregulatory hormone dynamics, and ultrastructural correlates) also will be extended to a subhuman primate model.